七例晚发型糖原贮积病Ⅱ型患者临床特征及基因突变分析  

Clinical features and genetic analysis of 7 patients with late-onset glycogen storage disease typeⅡ

作　　者：杨娟[1] 操基清[2] 刘振华[1] 詹益鑫[3] 梁颖茵[2] 莫桂玲[3] 李亚勤[2] 孙毅明[4] 李敏子[1] 利婧[2] 张成[2] 

机构地区：[1]南方医科大学珠江医院神经内科,广州510282 [2]中山大学附属第一医院神经科,广州510080 [3]广州金域医学检验中心有限公司,广州510330 [4]中山大学附属第一医院保健科,广州510080

出　　处：《中国现代神经疾病杂志》2014年第5期405-410,共6页Chinese Journal of Contemporary Neurology and Neurosurgery

基　　金：国家自然科学基金-广东省联合基金资助项目(项目编号:U1032004);国家自然科学基金资助项目(项目编号:30870851);国家自然科学基金资助项目(项目编号:81271401);国家科技支撑计划项目(项目编号:2012BAI09B04);国家科技重大专项课题-重大新药创制(项目编号:2011ZX09307-001);广东省科技计划项目(项目编号:2011A030400006);广东省人口和计划生育委员会科技项目(项目编号:2009208);广东省人口和计划生育委员会重点项目(项目编号:2010102)~~

摘　　要：目的分析4个家系7例晚发型糖原贮积病Ⅱ型患者之临床特点和基因型,以提高对该病的认识。方法收集患者临床资料,并行酸性α-葡糖苷酶(GAA)基因突变分析。结果 7例患者分别来自4个家系,年龄13～31岁、发病年龄6～17岁、初诊年龄12～29岁、明确诊断年龄12～30岁;首发症状为肢带肌萎缩、无力,酸性α-葡糖苷酶活性0～5.27 nmol/(mg·h)。GAA基因突变分析共发现14种突变,其中2种为新突变位点(Q81X和c.1355_1356delC)、2种假缺陷等位基因位点(G576S和E689K)、8种多态性位点和2种已知的致病突变位点(W746C和D645E)。结论中国大陆地区对糖原贮积病Ⅱ型之诊断时间存在明显的延误,提高医务人员的认识和理解将有助于改善患者预后。在明确诊断糖原贮积病Ⅱ型或判断预后时,应结合临床病史、酸性α-葡糖苷酶活性检测和GAA基因突变分析。糖原贮积病Ⅱ型之临床表型具有异质性,在GAA基因型相同的情况下,同一家系的不同个体间可存在疾病进程和严重程度的差异。Objective In order to make a well understanding on glycogen storage disease type Ⅱ （GSD Ⅱ）, this paper explored clinical features and genetic analysis of 7 patients with late-onset glycogen storage disease type Ⅱ. Methods Clinical data of 7 patients with late-onset glycogen storage disease type Ⅱ were collected and acid α-glucosidase （GAA） gene sequencing was performed. Results Seven patients who belong to 4 families were at the age of 13-31 years old. The first symptom occurred at 6-17 years old, and the age at first and definitive diagnosis was 12-29 and 12-30 years old, respectively. The initial symptoms were mostly related to limb girdle muscular atrophy and weakness. The GAA activity ranged from 0 to 5.27 nmol/（mg, h）. Sequencing analysis revealed 14 sequence variants, including 2 novel mutations （Q81X and c.1355_1356de1C）, 2 pseudodeficiency alleles （G576S and E689K）, 8 polymorphic loci, and 2 sequence variants previously related with glycogen storage disease type Ⅱ pathogenesis （W746C and D645E）. Conclusions Due to the apparently diagnostic delay, prognosis of patients with glycogen storage disease type Ⅱ could be improved by increasing the clinician＇s awareness of the disease. It is essential to combine clinical history with GAA activity and GAA gene analysis when we make a definitive diagnosis of glycogen storage disease type Ⅱ. Though siblings share the same set of GAA mutations, the phenotype regarding the course and severity of disease could vary substantially.

关 键 词：糖原贮积病Ⅱ型 α葡糖苷酶类 基因 突变 

分 类 号：R589.1[医药卫生—内分泌]